LAROTID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAROTID (LAROTID).
Larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) A, B, and C. It inhibits TRK kinase activity by binding to the ATP-binding site, leading to inhibition of downstream signaling pathways, which results in reduced cell proliferation and tumor growth in tumors with NTRK gene fusions.
| Metabolism | Larotrectinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. |
| Excretion | Renal: 70-80% unchanged by glomerular filtration and tubular secretion; Biliary/Fecal: <10% as inactive metabolites. |
| Half-life | 30 minutes; prolonged in renal impairment (up to 20 hours in anuria). |
| Protein binding | 20% bound, primarily to albumin. |
| Volume of Distribution | 0.3-0.4 L/kg; indicates distribution into total body water with low tissue penetration. |
| Bioavailability | Oral: 75-90% (variable with food); IM: 100%. |
| Onset of Action | Oral: 30-60 minutes; IM/IV: immediate (within 5 minutes). |
| Duration of Action | 4-6 hours; may be extended in renal impairment. |
Larotrectinib 100 mg orally twice daily, with or without food, for adult patients.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 75 mg twice daily. Larotrectinib has not been studied in patients with end-stage renal disease requiring hemodialysis. |
| Liver impairment | For Child-Pugh Class A (mild) or Class B (moderate) hepatic impairment, no dose adjustment. For Child-Pugh Class C (severe), reduce dose to 75 mg twice daily. |
| Pediatric use | Body surface area (BSA)-based dosing: 100 mg/m², up to a maximum of 100 mg, orally twice daily. Administer with or without food. |
| Geriatric use | No specific dose adjustment in elderly patients beyond standard dosing. Monitor renal function and adjust if severe impairment present. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LAROTID (LAROTID).
| Breastfeeding | Amoxicillin is excreted into breast milk in small amounts (M/P ratio approximately 0.01-0.04). It is considered compatible with breastfeeding by the American Academy of Pediatrics. Potential risks include diarrhea, candidiasis, or allergic reaction in the infant. Monitor for these effects. |
| Teratogenic Risk | Larotid (amoxicillin) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate well-controlled studies in pregnant women exist. However, amoxicillin is widely used in pregnancy without evidence of teratogenicity. First trimester: Low risk, no documented malformations. Second trimester: Safe for treating infections. Third trimester: No specific risks, but use only when clearly needed. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | Neurologic adverse reactions (including dizziness, gait disturbance, and paresthesia), hepatotoxicity, prolonged QT interval, embryo-fetal toxicity. |
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| Fetal Monitoring | No specific monitoring required beyond standard prenatal care. Monitor for allergic reactions, superinfection, and gastrointestinal disturbances. In prolonged therapy, monitor renal and hepatic function. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies have not shown impaired fertility. |